Outcomes of daratumumab, pomalidomide, and dexamethasone (DPd) followed by high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) in patients with relapsed/refractory myeloma RRMM.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20508-e20508
Author(s):  
Al-Ola A. Abdallah ◽  
Ajoy Dias ◽  
Hameem I Kawsar ◽  
Ghulam Rehman Mohyuddin ◽  
Monia Sigle ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Common Grade ◽  
Grade 3 ◽  
The University

e20508 Background: The number of therapeutic options for patients with RRMM has increased significantly. Our institute treated a series of patients with induction therapy consisting of DPd followed by HDCT/ASCT. We present the early outcomes of these patients. Methods: We treated 16 patients with RRMM at the University of Kansas Health System between May 2016 and October 2019, with DPd as induction therapy followed by HDCT/ASCT. DPd was administered as Daratumumab 16 mg/kg weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks; pomalidomide was dosed at 4 mg orally on days 1-21 of a 28-day cycle; and dexamethasone 20 or 40 mg weekly. Responses were evaluated using the 2016 International Myeloma Working Group (IMWG) criteria. Results: Patients had received a median of two prior regimens. Out of the 16 patients: 81% received ASCT prior to this treatment. In addition, 75%,81% and 68% were refractory to proteasome inhibitors (PI), immunomodulatory agents (IMiDs), and double refractory to IMiDs and PI, respectively. Median time from diagnosis to treatment was 12 months. Median number of DPd cycles received was 4 cycles. A median follow-up of 27 (9-39) months, the overall response rate (ORR) after induction treatment with DPd was 100%. ORR on day 100 post ASCT was 100%, 65% achieved ≥CR, and 81% achieved ≥VGPR. There was no treatment related mortality on day 100. Median progression free survival was 34 months (95%, CI = NA), median overall survival was not reached. The most common grade ≥ 3 adverse events were thrombocytopenia 53%, anemia 40%, neutropenia 53%. Conclusions: DPd as induction therapy followed by HDCT/ASCT demonstrated deep, durable, and clinically meaningful responses with manageable safety profile in patients with RRMM. [Table: see text]

Gemcitabine, cisplatin and methylprednisolone (GEM-P) in patients with T-cell lymphoma: Results from The Royal Marsden Hospital

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17507-17507
Author(s):  
H. Arkenau ◽  
M. Trumper ◽  
B. Sirohi ◽  
G. Chong ◽  
I. Chau ◽  
...  
Keyword(s):  
T Cell ◽  
Progression Free Survival ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Neutropenic Sepsis ◽  
Royal Marsden Hospital ◽  
Previously Treated ◽  
Grade 3 ◽  
Number Of Cycles

17507 Background: There is a need for novel, effective therapies for T-cell non-Hodgkin’s lymphoma (NHL). The combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) has shown activity in patients (pts) with relapsed Hodgkin’s disease and NHL (Chau I et al. Br J Haematol 2003, Baetz T et al. Ann Oncol 2003). We report a single institution retrospective analysis of GEM-P for pts with T-cell NHL. Methods: Sixteen pts with T-cell NHL treated at the Royal Marsden Hospital between June 2001 and March 2005 with GEM-P (gemcitabine 1 g/m2 D1, 8, 15; cisplatin 100 mg/m2 D15; methylprednisolone 1 g D1–5, repeated every 28D) were identified. Results: 16 pts (9 males and 7 females) were analysed. Histological subtypes were: angioimmunoblastic (n = 5), T-cell enteropathy (n = 2), NK/T cell nasal-type (n = 2), T-cell anaplastic (n = 3) and peripheral T-cell unspecified (n = 3). Median age was 55 years (range: 18–71 years), 69% had IPI-score ≥ 2 and 69% had stage III/IV disease. 15 /16 pts were pre-treated: median number of prior treatments: 1 (range: 0–4). At the start of GEM-P treatment pts presented with: primary refractory disease (n = 3), 1st relapse (n = 6), 1st relapse refractory (n = 3), 2nd relapse (n = 2) and 4th relapse (n = 1). Median time from diagnosis of T-cell NHL to start of GEM-P was 8.9 months(m) and median number of cycles given was 3 (range: 1–6). Of 16 evaluable patients, 3 pts (19 %) achieved complete remission (CR), 8 pts (50 %) achieved partial remission (PR), (ORR= 69%; CI-95% 41.4–89.0) and 5 pts (31%) progressed while on GEM-P. One pt received high dose chemotherapy (melphalan/etoposide) after CR to GEM-P. After a median follow up of 17.4m the mean progression free survival (PFS) was 9m (range 1.15–37.5). The median overall survival (OS) has not been reached and the survival probability at 1 year was 68.2% (95% CI: 40–85). The main grade 3/4 toxicities were myelosuppression (leucopenia 62%, neutropenia 62% and anaemia 12%) and required granulocyte colony stimulating factor (GCSF) in 3 pts with neutropenic sepsis and in 1 pt with neutropenia. Conclusion: GEM-P has encouraging efficacy with an acceptable toxicity profile in pts with previously treated T-cell NHL. [Table: see text]

scholarly journals Induction therapy and the role of stem cell transplantation in the treatment of myeloma multiplex in patients aged below 65 years

2011 ◽  
Vol 139 (suppl. 2) ◽  
pp. 103-109
Author(s):  
Dragana Stamatovic ◽  
Ljiljana Tukic ◽  
Bela Balint
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Conditioning Regimen ◽  
Proteasome Inhibitors ◽  
High Dose Chemotherapy ◽  
High Risk Group ◽  
Induction Treatment ◽  
High Dose

Therapeutical concept for myeloma mulitplex (MM) patients has been significantly improved over the previous years. As in other haematological malignancies, in MM also, induction treatment goal is to achieve complete remission (CR) of the disease. The importance of CR on overall survival (OS) in MM was first estimated in the high dose chemotherapy (CT) with autologous stem cell transplantation (ASCT). Induction treatment with 3-6 cycles of combined CT based on Dexamethason (VAD) following with one or two courses of high doses of Melphalan with ASCT leads to 20-40% CR and 40-55% CR/VGPR with median survival of 4-5 years. These are significantly better results compared to previous conventional therapy, and considering such findings, ASCT became the treatment of choice for MM patients aged below 65 years. The introduction of novel agents, such as immunomodulatory drugs (Thalidomid, Lenalidomid) and proteasome inhibitors (Bortezomib) into induction therapy have improved treatment of MM patients even more. The combination of Dexamethason with Thalidomid, Bortezomib or Lenalidomid, on the average in 3-4 cycles, arises the level of CR/ VGPR (very good partial response) even to 60-75%. Bortezomib based regimens are recommended in the treatment of ?high risk? group of patients with MM. Recommended conditioning regimen is 200 mg/m2 of Melphalan. If either CR or VGPR is not achieved, recommendation is to perform the second ASCT as a part of ?tandem?concept. Thalidomid applied as a ?maintenance therapy? after ASCT may prolong OS. Until now, allogeneic ASCT, as the first line treatment for MM patients aged below 65 years, has been applied only in clinical trials.

Lenalidomide Combined With Cyclophosphamide and Dexamethasone Is Effective and Well Tolerated Induction Treatment For Newly Diagnosed Myeloma Patients Of All Ages

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 540-540 ◽  
Author(s):  
Charlotte Pawlyn ◽  
Annamaria Brioli ◽  
Walter Gregory ◽  
Samantha Hinsley ◽  
Jindriska Lindsay ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Induction Therapy ◽  
Proteasome Inhibitors ◽  
Sensory Neuropathy ◽  
Induction Treatment ◽  
Second Primary ◽  
High Dose ◽  
Advisory Committees ◽  
Educational Grant ◽  
Grade 3

Abstract Lenalidomide is an excellent option for induction therapy for myeloma due to its oral administration and lack of significant peripheral neuropathy when compared with bortezomib and thalidomide. Triplet combinations containing novel agents have been shown to be more effective than doublets or single agents, whilst there is little additive benefit from quadruplets without increasing toxicity. Lenalidomide has been combined in the older population with melphalan and prednisolone but this has raised concerns due to the rates of cytopenias and the possibility of increasing second primary malignancies (SPMs). We have studied the combination cyclophosphamide, lenalidomide and dexamethasone (CRD) in relapsed patients (Morgan et al, BJH, 2007; Schey et al BJH, 2010) and found it well tolerated and highly effective (ORR 65-81%), giving better responses than would be expected with RD alone. We therefore designed a trial, Myeloma XI, which compared responses to cyclophosphamide, lenalidomide and dexamethasone (CRD) with cyclophosphamide, thalidomide and dexamethasone (CTD) given to maximum response or intolerance. Younger/fitter patients received cyclophosphamide 500mg (p.o. D 1,8), lenalidomide 25mg (p.o. D1-21) and dexamethasone 40mg (p.o. D1-4, D12-15) as part of a 28 day regimen on the intensive pathway whilst older/less fit patients received attenuated doses of dexamethasone, 20mg (p.o. D1-4, D15-18) on the non-intensive pathway (CRDa). Patients achieving no response (NC or PD) after a minimum of 4 cycles received further therapy with a triplet composed of cyclophosphamide, bortezomib and dexamethasone (CVD), those with a suboptimal response (MR or PR) were randomised to either no further therapy or to CVD and those achieving ≥ VGPR received no further induction. Younger/fitter patients went on to receive high dose melphalan (HDM) plus ASCT whereas older/less fit patients did not. The trial is ongoing and to date has recruited 1310 patients to the intensive pathway (650 CRD vs 660 CTD, median age 61 years, range 28-75) and 1058 to the non-intensive (531 CRDa vs 527 CTDa, median age 74 years, range 51-89). The overall response rate (≥PR) at the end of lenalidomide induction for those currently evaluable in the intensive pathway is 83% (CR 16%, VGPR 42%, PR 24%, n=389) and in the non-intensive pathway 73% (CR 17%, VGPR 34%, PR 21%, n=289). Given that those patients with <VGPR undergo a further randomisation to possible further induction therapy with bortezomib we anticipate, based on previous analysis, that this will translate into rates of ≥VGPR at the end of induction of 64% and 57% respectively which compares very favourably to response rates seen when immunomodulatory drugs and proteasome inhibitors are given in combination. CRD was well tolerated with patients receiving a median of 5 cycles in the intensive pathway and 6 cycles in the non-intensive pathway. 61% (236/389, intensive) and 74% (206/279, non-intensive) of patients required a dose reduction of at least one drug but this did not affect their ability to remain on treatment with only 5% (18/389) and 11% (30/279) respectively failing to complete the minimum number of cycles stipulated in the protocol due to toxicities. Dose density was maintained with 62% of patients receiving all doses with no delay. Overall 12% of treatment cycles given had a delay either between or within cycles but of these 93% were delays of less than 3 days. In the lenalidomide treated population available for safety analysis (n=907) the most common grade 3/4 toxicities were cytopenias with slightly higher rates seen in the older/less fit population (neutropenia 20% vs 33%, thrombocytopenia 5% vs 10% and anaemia 10% vs 17%). Only 1.1% of patients developed grade 3/4 peripheral motor or sensory neuropathy and there were a total of 22 PEs reported (2%) with no difference between the pathways. In the randomised population treated with lenalidomide, (n=1181) treatment related mortality was 0.4% and the incidence of SPMs was low at 0.7% with a median follow up of 1.36 years which may reflect the significantly lower mutagenicity of cyclophosphamide than melphalan. These preliminary results suggest that the combination of lenalidomide, cyclophosphamide and dexamethasone is effective as induction treatment and has a good safety profile in myeloma patients of all ages. On behalf of the NCRI Haemato-oncology subgroup Disclosures: Pawlyn: Celgene: travel support, unrestricted educational grant Other. Off Label Use: Lenalidomide and vorinostat as maintenance treatment for myeloma. Brioli:Celgene: Honoraria, unrestricted educational grant Other. Gregory:Celgene: unrestricted educational grant Other. Hinsley:Celgene: unrestricted educational grant Other. Lindsay:Celgene: unrestricted educational grant Other. Cook:Celgene: unrestricted educational grant Other. Milligan:Celgene: unrestricted educational grant Other. Chapman:Celgene: unrestricted educational grant Other. Owen:Celgene: unrestricted educational grant Other. Drayson:Celgene: unrestricted educational grant Other. Russell:Celgene: unrestricted educational grant Other. Jackson:Celgene: Honoraria, unrestricted educational grant Other. Davies:Celgene: Honoraria, Speakers Bureau, unrestricted educational grant Other; Jansen: Honoraria, Speakers Bureau. Morgan:Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, unrestricted educational grant Other; Merck: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Complete response (CR) to ifosfamide, gemcitabine, and vinorelbine (IGEV) and outcome in relapsed/refractory Hodgkin's lymphoma (HL) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8568-8568
Author(s):  
A. Anastasia ◽  
R. Mazza ◽  
L. Giordano ◽  
M. Balzarotti ◽  
M. Magagnoli ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Disease Status ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cox Proportional Hazard ◽  
Kaplan Meier

8568 Background: High dose chemotherapy with autologous stem cells transplant (ASCT) is the gold standard in patients with relapsed/refractory HL. Response to induction chemotherapy (chemosensitive patients) plays a major role in prognosis, however the role of CR status after induction therapy has not been established. Methods: One hundred twenty one patients with relapsed/refractory HL received 4 courses of IGEV followed by single (N=59) or tandem (N=19) ASCT (Santoro et al., Haematologica 92, 2007). Response to IGEV was evaluated by Cheson criteria (1999).The aim of this study was to evaluate the role of CR versus no-CR to IGEV induction therapy on the outcome in terms of progression free survival (PSF) and overall survival (OS). Statistical analysis was performed by using the Kaplan-Meier method and Cox proportional hazard model. Results: IGEV induced an overall response rate of 75% with 46% of CR. In the univariate analysis favourable factors for outcome were CR vs no-CR to IGEV (PFS: p <0.001, OS: p 0.002), A vs B symptoms (PFS: p 0.003; OS: p 0.05), limited vs advanced stage (PFS: p 0.03; OS: p 0.03), and 1 vs≥2 previous chemotherapy lines (PFS: p 0.03, OS: p 0.02); response to last therapy (relapsed vs refractory) influenced PFS (p 0.03) but not OS (p 0.70). The multivariate analysis confirmed the favourable prognostic role of CR to IGEV (PFS HR: 2.5, CI 95%:1.3; 4.6 - OS HR 2.3, CI 95%:1.1;4.8) and of the number of previous chemotherapy lines (PFS HR:1.8, CI 95%:1.0;3.2 - OS HR 2.1, CI 95%:1.1;3.9). Conclusions: According to our data, we conclude that: 1. CR to IGEV is the strongest indicator of outcome in relapsed/refractory HL. 2. Achievement of CR to IGEV overcomes the role of initial disease status. 3. Efforts are warranted to increase the CR rate by induction therapy. No significant financial relationships to disclose.

Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): Impact of cytogenetics in MM-003.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8528-8528
Author(s):  
Hartmut Goldschmidt ◽  
Meletios A. Dimopoulos ◽  
Katja C. Weisel ◽  
Philippe Moreau ◽  
Martha Lacy ◽  
...  
Keyword(s):  
High Risk ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Open Label ◽  
High Dose Dexamethasone ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Intent To Treat

8528 Background: RRMM patients (pts) who fail lenalidomide (LEN) and bortezomib (BORT) have poor prognosis. High-risk cytogenetics predict shorter survival. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT and high-risk cytogenetics. MM-003 is an open-label, multicenter, phase III trial comparing POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT treatment (Tx) and have progressed on their last therapy. Methods: Pts must have been refractory to the last prior Tx (progressive disease [PD] during or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-day cycles). Tx continued until PD or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS and AEs. This analysis examined pts meeting modified high-risk cytogenetic criteria—del(17p13) and/or t(4p16/14q32). Results: 302 pts received POM + LoDEX, and 153 pts received HiDEX. 225 and 107 pts, respectively, were evaluable for cytogenetics. Baseline characteristics were similar. Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX, regardless of cytogenetic risk (Table). The most common grade 3/4 AEs were neutropenia, anemia, and infection (Table). Discontinuation due to AE was low: 4% vs. 6% (high risk) and 10% vs. 4% (standard risk). Conclusions: Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX in pts with cytogenetically-defined high-risk disease, consistent with results from the intent-to-treat population. Tolerability was acceptable. POM + LoDEX should be considered a new Tx option in pts failing LEN and BORT. Clinical trial information: NCT01311687. [Table: see text]

Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM) Patients with Dialysis-Dependent Renal Failure Is Effective but Carries High Rates of Toxicity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 954-954 ◽  
Author(s):  
Lisa Chodirker ◽  
Joseph R. Mikhael ◽  
Keith Stewart ◽  
Andrew Winter ◽  
Donna E. Reece ◽  
...  
Keyword(s):  
Renal Failure ◽  
Survival Data ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Dexamethasone ◽  
Cd34 Cells ◽  
Common Grade ◽  
Grade 3

Abstract Background: Studies have shown ASCT to be feasible in MM patients (pts) with renal impairment but there are limited data supporting this approach in pts with severe dialysis-dependent renal failure. Patients and Methods: This is a single institution retrospective review of all MM pts who were receiving regular dialysis support at the time of ASCT. Pts with light chain amyloidosis were excluded. Results: From 1998–2006, 22 hemodialysis patients underwent ASCT at our institution. Median age at transplant was 54.3 years (range, 39.4–64.7); 17(77%) pts were male; 17(76%) Salmon Durie stage II–IIIB . MM subtypes: light chains only 9(41%), IgG 8(36%), IgA 4(13%), IgD 2(9%). All pts received high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX alone). High dose therapy consisted of Melphalan (MEL) 200 mg/m2 in 18 pts and MEL 140 mg/m2 in 3 pts. A median of 5.87 X 106 (range, 2.47–51.0) CD34+ cells/kg were collected using cyclophosphamide 2.5 g/m2 + GCSF 10ug/kg/day. Median days to discharge were 19 (range, 14–59). Hematologic toxicity: Of 20 pts with transfusion data available, 14(70%) required RBC and 18(90%) platelet transfusions. Median time to engraftment for neutrophils was 11 days (range, 9–14) and for platelets 13 days (range, 8–17). All patients developed febrile neutropenia. Non-hematologic toxicity (data available in 21 pts): cardiac 13(62%) (arrhythmias, myocardial infarction, CHF), hypotension 6(29%), neurologic 6(29%)(seizure, altered sensorium), infections 6(29%), diarrhea 6(29%), electrolyte imbalances 4(19%) and bleeding 3(14%). Most common grade 3–4 toxicities included mucositis 17(81%), cardiac 12(57%)(most due to atrial arrhythmias), bleeding 3(14%)(epistaxis, hematemesis, tissue hematomas) and infections 3(14%)(CMV, bacteremia, Candidemia). Transplant related mortality (TRM) was 13.6% (3/22) with causes of death including disseminated candidiasis (2) and CMV infection. Responses: Partial responses (PR) were achieved in 18/22 pts. Progression free survival (PFS) from transplant was 22.3 months (95% CI 15–45.6). Three pts (13%) became dialysis-independent (all within 30 days post-transplant). At a median follow-up of 29.6 months (range 0.8–79.6), 10/22 (45%) of patients are alive. Estimated median overall survival from date of transplant was 60 months (95%CI 20.2–79.6) with a 5-year survival probability of 53.2%. Discussion: ASCT in dialysis-dependent MM pts achieves response rates and survival data comparable to that of non-dialysis populations. However, it carries increased toxicity, prolonged median days to discharge (19 days vs. institutional mean of 14 days) and a higher TRM (13.6% vs. institutional mean of 1.6%). The higher rates of cardiac and neurological toxicities enforce the need for pre-transplant identification of pts with co-morbidities, for consideration of dose reduction and risk factor optimization.

Brentuximab Vedotin (SGN-35) in Patients with Relapsed/Refractory CD30-Positive Hematologic Malignancies without Prior High-Dose Chemotherapy and Stem Cell Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2743-2743 ◽  
Author(s):  
Achim Rothe ◽  
Stephanie Sasse ◽  
Helen Goergen ◽  
Dennis A. Eichenauer ◽  
Andreas Lohri ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Refractory Disease ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Initiation Of Therapy

Abstract Abstract 2743 Background: Based on the impressive results of two pivotal phase II trials, the CD30 targeting antibody-drug conjugate brentuximab vedotin (SGN-35) was approved for the treatment of relapsed Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) by the Food and Drug Administration (FDA) in 2011. Recently, we reported the experience of the German Hodgkin Study Group (GHSG) with brentuximab vedotin as single agent in 45 patients suffering from refractory or relapsed CD30-positive HL. In this cohort with a median age of 35 years and a median number of four prior chemotherapy regimens, overall survival (OS) and progression-free survival (PFS) at 12 months were 83% (95%-CI: 72%-95%) and 43% (95%-CI: 28%-58%), respectively. Interestingly, 10 of 17 patients considered very high-risk (59%) who had primary refractory disease or early relapse and refractory disease prior to brentuximab vedotin treatment, achieved an objective response, which was comparable to the overall response rate of 60% for the whole cohort (Rothe et. al., Blood, July 2012). Since very limited data is available on relapsed or refractory HL patients who received brentuximab vedotin without prior high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), we have expanded our analysis. Methods: Since March 2010, the GHSG and associated centres have treated patients with refractory or relapsed HL or relapsed ALCL with brentuximab vedotin. In addition to six patients included in our previous analysis, we identified 10 further patients who had not undergone prior HDCT and SCT and were treated with brentuximab vedotin. All patients had histologically confirmed CD30-positive lymphoma and were treated within a named patient program (NPP). All participants gave written informed consent in accordance with the Declaration of Helsinki. Patients received a 30-minute infusion of brentuximab vedotin dosed at 1.8mg/kg body weight every three weeks. Response was defined according to the revised response criteria for malignant lymphoma. Overall survival (OS) was defined as the time from the initiation of therapy to death from any cause. Progression-free survival (PFS) was measured from initiation of therapy to progression, relapse, or death from any cause. Results: In total, 16 patients with HL (n=14) or ALCL (n=2) with a median age of 48.5 years and a median number of three prior chemotherapy regimens were analyzed. Reasons for ineligibility for HDCT and autologous SCT prior to treatment with brentuximab vedotin were refractory disease (n=11), comorbidity (n=4) and unknown reasons (n=1). Treatment with brentuximab vedotin resulted in an objective response in 11 patients (69%), including five complete remissions. Noteworthy, six of the 11 patients with chemotherapy refractory disease and all four patients with significant comorbidity achieved an response. Six patients received a consolidating HDCT followed by autologous (n=4) or allogeneic (n=2) SCT after brentuximab vedotin treatment. OS and PFS at 12 months were 68% (95%-CI: 40%-95%) and 22% (95%-CI: 0%-48%), respectively. Conclusion: This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in patients with heavily pre-treated CD30-positive malignancies. Moreover, we present the first data indicating therapeutic efficacy of brentuximab vedotin as reinduction therapy in chemotherapy-refractory HL and ALCL patients before HDCT and ASCT. Disclosures: Engert: Millenium The Takeda Oncology Company: Honoraria.

Mature Results From ECOG Study E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for Previously Untreated Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 153-153 ◽  
Author(s):  
Brad S. Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
David T. Yang ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Treatment Plan ◽  
Induction Treatment ◽  
High Dose ◽  
Group Setting ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 153 Introduction Modified R-hyperCVAD is a well-tolerated induction regimen with a high response rate in MCL. We hypothesized that the incorporation of bortezomib (Velcadea) into this regimen would enhance the complete response rates. We further hypothesized that the addition of maintenance rituximab (MR) would improve remission duration. The new regimen, VcR-CVAD with MR, was tested for safety and efficacy in the Eastern Cooperative Oncology Group. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0–2, and adequate end organ function. The treatment plan included: bortezomib 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs × 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1–4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients could elect to receive high dose chemotherapy and autologous stem cell transplantation (SCT) off protocol rather than MR. The primary endpoint of the trial was the CR rate, defined as PET-negative, marrow-negative, to VcR-CVAD induction therapy. Results Seventy-five eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40–76), 58M:17F, 92% stage III/IV, and 40% with elevated LDH. MIPI risk distribution included 37% low, 36% intermediate, 19% high, 8% unknown. Sixty-eight patients (91%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), and patient preference (2). The ORR was 97% (73/75), CR rate 68% (51/75) and PR rate 29% (22/75). Of the 22 PR patients, 11 were so coded due to no bone marrow evaluation and/or PET imaging post therapy. The CR rate in the 64 completely restaged patients was 80%. Forty-four patients proceeded to protocol planned MR while 22 patients received SCT consolidation off protocol. With a median follow up of 3.6 years, the 3-yr PFS for the MR cohort (n = 44) and entire cohort (n = 75) are 73% and 74%, respectively. OS at 3-yrs is 88%, with no difference between MR and SCT patients. The major toxicity of the induction treatment regimen was expected myelosuppression. Grade 3–4 non-hematologic toxicities were rare. No patients developed grade 3–4 neuropathy. There were no serious toxicities during MR. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall OR (97%) and CR rates (68%) in a representative MCL patient population treated in a cooperative group setting. The 3-yr PFS (74%) and OS (88%) are highly encouraging. Remissions in patients receiving MR were as durable as patients receiving SCT consolidation. The value of bortezomib, when added to conventional chemotherapy, is currently being tested in a randomized intergroup trial (E1411). Disclosures: Kahl: Genentech: Consultancy, Research Funding; Roche: Consultancy; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as frontline treatment of mantle cell lymphoma. Smith:Millennium: Research Funding. Advani:Genentech: Research Funding. Horning:Genentech: Employment; Roche: Equity Ownership.

Velcade, Intravenous Cyclophosphamide and Dexamethasone (VCD) Induction for Previously Untreated Multiple Myeloma (German DSMM XIa Trial).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 131-131 ◽  
Author(s):  
Hermann Einsele ◽  
Peter Liebisch ◽  
Christian Langer ◽  
Martin Kropff ◽  
Hannes Wandt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Research Funding ◽  
Response Rate ◽  
Induction Treatment ◽  
High Dose ◽  
Prognostic Impact ◽  
Short Period ◽  
Grade 3 ◽  
High Dose Melphalan

Abstract Abstract 131 Introduction. Autologous stem cell transplantation (ASCT) after cytoreductive induction is considered standard of care for younger patients (pts) with multiple myeloma (MM). The previous standard of induction, the Vincristin-Adriamycin-Dexamethasone (VAD) combination, achieves inferior results compared with induction regimens which combine the proteasome inhibitor Velcade (V = Bortezomib) with Dexamethasone (D)(=VD) and a cytostatic drug such as Doxorubicin (PAD = VD plus Doxorubicin). Velcade-based induction therapy was shown to translate into better myeloma control after high dose melphalan and to lead to prolonged progression-free survival. In order to find a more efficacious and safer drug combination for induction therapy in MM, we tested the combination of Velcade with Cyclophosphamide and Dexamethasone (VCD). Methods. This trial was designed as an open, prospective, multi-center, uncontrolled, combined phase II/III study. As previously reported (Kropff M et al., Ann Hematol 2009), in the first 30 pts the optimal dose of iv Cyclophosphamide in combination with V and D was defined as 900 mg/m2 on d1. Between 03/2006 and 03/2009 we enrolled an additional 370 pts up to 60 years of age with untreated MM to receive three 3-week cycles of induction treatment with V 1.3 mg/m2 iv d1,4,8,11; D 40 mg/d orally d1,2,4,5,8,9,11,12; and C 900mg/m2 iv d1 before scheduled high dose melphalan and ASCT. The primary endpoint of the study is response rate on day 63 after 3 cycles of VCD according to EBMT and IMWG criteria. Results. Final data from 400 pts from 39 German centers will be presented at the meeting. In the currently evaluable 300 pts (mean age 52.3 years; 1.7% stage I, 21.3% stage II, 77.0% stage III) molecular cytogenetic analysis showed a prevalence of 13q- in 38%, of t[4;14] in 13% and of 17p- in 12% of pts (no changes in 35%). All 300 pts (88.3% of whom completed three cycles) were included in the intent-to-treat analysis. Overall response rate (ORR = CR+PR) was 84%, with 10% CR and 74% PR, 5.7% MR, 7.3% NC and 2.3% PD. The negative prognostic impact of 13q- or t[4;14] was abrogated (ORR normal 87.3%, 13q- 83.7%, t[4;14] 90.0%), the unfavorable influence of p53 loss in the 17p- subgroup was still detectable (ORR 69.2%) but this did not reach statistical significance. VGPR rates will be reported at the meeting. Serious adverse events were documented in 78/300 (26.0%) patients. Death rate was remarkably low (1.3%, of which one was not related to the trial medication). 155/300 (52%) of pts experienced grade 3/4 non-serious AEs and of these leucopenia (93/300 pts= 31%), thrombocytopenia (7%), neutropenia (6%), anaemia (5%) were the most frequent events. 80 AEs grade 3 or 4 and 45 SAEs were of infectious origin and occurred in 47/300 pts. 80/130 SAEs (61.5%) were at least possibly related to Velcade. 101/300 pts (34%) developed episodes of peripheral neuropathy. PNP was grade 1 in 62/300 pt (20.7%), grade 2 in 31/300 pt (10.3%) and grade 3 in 7/300 pts (2.3%). Conclusion. This analysis demonstrates that proteasome inhibition by Velcade in combination with Dexamethasone and iv Cyclophosphamide (VCD) is an induction regimen for newly diagnosed MM which is highly effective in a short period of time, has a rather low toxicity profile and is feasible for administration in an outpatient setting. Based on these characteristics, VCD qualifies to become a new standard for MM induction therapy. Disclosures: Einsele: OrthioBiotech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Bortezomib is licensed as monotherapy for use in relapsed/refractory MM and in combination with melphalan/Prednisone in the first-line treatment of MM pts ineligible for HD-MEL and ASCT. . Liebisch:OrthoBiotech: Consultancy, Honoraria. Langer:OrthoBiotech: Consultancy. Kropff:OrthoBiotech: Consultancy, Honoraria. Kröger:OrthoBiotech: Honoraria. Ostermann:OrthoBiotech: Honoraria. Mügge:OrthoBiotech: Honoraria. Wolf:OrthoBiotech: Honoraria. Gramatzki:OrthoBiotech: Consultancy, Honoraria. Maschmeyer:OrthoBiotech: Travel Grant. Sezer:OrthoBiotech: Consultancy, Honoraria. Heidemann:OrthoBiotech: Honoraria. Jäger:OrthoBiotech: Honoraria. Dechow:Celgene: Research Funding. Simon:OrthoBiotech: Honoraria. Straka:OrthoBiotech: Consultancy, Honoraria, Research Funding. Fingerle-Rowson:orthoBiotech: Employment. Knop:OrthoBiotech: Honoraria.

High-Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Transplantation (AHCT) for Non-Hodgkin’s Lymphoma (NHL) in Patients over 65 Years of Age.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3059-3059
Author(s):  
Chitra Hosing ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Uday Popat ◽  
Daniel Couriel ◽  
...  
Keyword(s):  
Median Time ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Entire Cohort ◽  
Grade 3

Abstract High-dose chemotherapy followed by AHCT is the treatment of choice for relapsed NHL. Often this therapy is not offered to patients over 65 yrs of age because of concerns regarding their ability to tolerate “aggressive therapy”. We present a retrospective analysis of 99 consecutive pts. who underwent AHCT for NHL at our institution from 6/96–3/06. RESULTS: Median age at AHCT was 68 yrs (range, 65–83). Seventy percent were males. Most common histologies were DLCL (55%), MCL (15%), and FL grades 1–3 (15%). Median number of chemoregimens administered prior to AHCT were 2 (range, 1–6). Median IPI score at AHCT was 1 (range, 0–4). Majority of patients (99%) had a ECOG PS score of < 2 prior to AHCT. Forty-four percent pts were in CR/CRu, 45% were in PR, and 11% had PD/SD. The preparative regimen comprised of BEAM (35%), BEAM/rituximab (53%), and Cy/TBI +/− rituximab (10%). Median hospital stay was 23 days (range, 6–85) for AHCT with 38% requiring readmission within the first 100 days. Source of progenitor cells was HPC-A in 89%. Median CD34+ cell dose infused/kg was 4.4 x 106 (0.1–32.2). All patients engrafted. Median time to reach ANC ≥ 500/mm3 was 10 days (range 7–47). Ten patients never achieved a platelet (PLT) count of 20,000/mm3. For the remaining 88 pts., median time to reach PLT ≥ 20,000/mm3 was 13 days (range, 6–375). Median number of PRBC units transfused were 4 (range, 0–50) and median number of PLT transfusions required were 4 (range, 0–35). Grade 3–5 RRT toxicity is summarized in Table. Table *RRT Grades 3–5 Age years (No.) 65–69 (58 pts) 70–75 (34 pts) > 75 (8 pts) *CTCAE ver 3.0 Toxicity Grade 3/4/5 3/4/5 3/4/5 Pulmonary (pnemonitis) 1/1/0 0/0/1 0/0/1 GI (diarrhea) 6/0/0 2/0/0 0/0/0 GI (mucositis/stomatitis) 6/0/0 0/0/0 1/0/0 GI (nausea) 0/0/0 0/0/0 1/0/0 Neurologic (confusion) 1/0/0 1/0/0 0/0/0 GU (inc creatinine) 1/0/0 2/0/0 0/0/0 Hepatic 1/1/0 1/0/0 0/0/0 Cardiovascular 3/0/0 1/0/0 1/1/0 Allergy (BCNU) 1/0/0 0/0/0 0/0/0 Skin rash 1/0/0 0/0/0 0/0/0 Fatigue/Bone pain 1/0/0 0/0/0 1/0/0 Cumulative TRM was 12 % (95% CI 6–22) at 3 yrs. Median follow-up among survivors is 26 mths (range, 1–115). OS at 3 yrs was 61% (95% CI 49–71) for the entire cohort. At 3 yrs the DFS was 48% (95% CI 33–61), 68% (95% CI 36–87), and 63% (95% CI 22–87) for DLCL, MCL and FL respectively. On univariate analysis IPI > 1, LDH > normal, and SD/PD at the time of AHCT were predictors of worse OS. Disease status at transplant and LDH > normal remained significant predictors for OS on multivariate analysis. Age, gender, histology, number of prior chemoregimens, time from diagnosis to AHCT, and conditioning regimen were not significant predictors of OS. Cause of death was disease progression/relapse in 60%. Eight patients developed sMDS/AML after AHCT. CONCLUSIONS: Patients over 65 yrs of age can undergo AHCT with acceptable toxicity and should be considered transplant candidates if they have chemosensitive disease and an IPI score of ≤ 1 at the time of AHCT.

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